Background-HIV transmission in stable serodiscordant couples may account for up to 60% of new HIV infections in Africa. Many HIV-discordant couples desire children, yet prevention programs that focus on abstinence and condoms do not accommodate fertility desire. Antiretroviral therapy (ART) dramatically reduces sexual HIV transmission and recent successes with oral and topical pre-exposure prophylaxis (PrEP) hold promise for reducing transmission without preventing conception. My research seeks to develop combination HIV prevention strategies that accommodate the importance of having children for people living with HIV. Candidate-Seven peer-reviewed manuscripts (five first-author) reflect my commitment to HIV clinical research and a research interest that evolved from basic to behavioral science. During infectious disease fellowship, my primary research mentor, Dr. David Bangsberg, and I have worked to formalize research questions in the novel field of reducing HIV transmission in the setting of desired pregnancy. I am applying for a 5-year K23 Career Development Award to acquire needed skills and experience to become an independent investigator developing periconception risk-reduction strategies for HIV-discordant couples in sub-Saharan Africa. Mentoring-In July 2011, I will complete fellowship and accept an appointment as Assistant in Medicine in the Massachusetts General Hospital Division of Infectious Diseases. Dr. Bangsberg is an experienced and committed mentor with a record of over 50 trainees and over 160 publications. He will be my primary mentor and has protected time to support me through his K24 mentoring award. He has helped me to assemble an expert mentoring team including Steve Safren (behavioral science), Connie Celum and Jared Baeten (infectious disease, epidemiology), Jenni Smit (HIV reproductive health), Abigail Harrison (qualitative methods), Jerome Kabakyenga (HIV, women's health), and Heather Ribaudo (biostatistics). Research-Using existing data, I will examine prevalence and predictors of pregnancy and fertility desire among HIV-discordant Ugandan couples on ART for treatment or PrEP for prevention. I will examine how fertility desire and pregnancy impact periconception adherence to ART or PrEP. These data and qualitative work will inform iterative development of a pilot intervention to reduce periconception HIV transmission risk for discordant couples. This work will be grounded in a dyadic framework of periconception HIV-risk behavior. Training-The research is supported by training in quantitative methods focusing on repeated measures;qualitative methods focusing on in-depth interviews;behavioral science;and structured mentoring in adherence measurement and intervention design. The project will provide pilot data and training to develop an intervention trial to reduce periconception risk, to be proposed as an R01. My commitment to addressing these questions, an outstanding mentoring team, strong institutional support, and an innovative research plan that addresses a public health priority all position me to achieve my goal of becoming an independent clinical investigator. PUBLIC HEALTH RELEVANCE: Each day there are 7400 new HIV infections worldwide, representing 5 new HIV infections for every 2 individuals who start treatment. In sub-Saharan Africa, up to sixty percent of these infections occur among stable, HIV-discordant couples (one partner is HIV-infected, the other is not). A growing body of literature shows that HIV-discordant couples choose to have children, yet current, established prevention strategies do not allow for conception. We propose to develop a reproductive counseling intervention to minimize transmission risk for HIV-discordant couples who choose to conceive. Bringing reproductive goals of HIV- discordant couples into the prevention agenda by communicating that it is possible to reduce periconception HIV transmission risk through carefully studied reproductive counseling interventions may address a substantial, previously unaddressed proportion of incident infections.